medwireNews: The benefits of extended prophylactic anticoagulation with rivaroxaban in acutely ill hospital patients are outweighed by an increased bleeding risk, shows a study in The New England Journal of Medicine.
The finding means it remains uncertain whether extended prophylactic anticoagulation may benefit such patients. A trial involving another new-generation anticoagulant, apixaban, also found an increased bleeding risk, while another comparing the current standard treatment, enoxaparin, against placebo suggested extended prophylaxis may only benefit certain subgroups.
The current randomized, controlled trial establishes that oral rivaroxaban 10 mg/day is noninferior to subcutaneous enoxaparin 40 mg/day for preventing thromboembolism during a standard treatment period. But even then, rivaroxaban comes at the price of an increased risk for bleeding.
The 8101 patients in the study received either enoxaparin or placebo injections for 10 days, along with oral placebo or rivaroxaban, respectively. During this period, 2.7% of patients from each group had an endpoint event - asymptomatic proximal or symptomatic venous thromboembolism.
The patients then received oral treatment only for a further 25 days, by the end of which the thromboembolism rates had risen to 4.4% in the rivaroxaban group versus 5.7% in the enoxaparin/placebo group - representing a significant 23% risk reduction with rivaroxaban, report lead researcher Alexander Cohen (King's College Hospital, London, UK) and colleagues.
However, patients' risk for major or clinically relevant nonmajor bleeding was significantly increased with rivaroxaban relative to enoxaparin at day 10 (2.8 vs 1.2%) and enoxaparin/placebo at day 35 (4.1 vs 1.7%).
The increased bleeding risk actually outweighed rivaroxaban's prophylactic benefits. The net rate of efficacy and safety endpoint events at day 10 was 6.6% in patients given the drug versus 4.6% in those given enoxaparin, which was a significant difference. Likewise, the rates with rivaroxaban versus placebo at day 35 were 9.4% versus 7.8%.
Cohen et al note that many patients in their trial had risk factors for bleeding, such as older age, impaired renal function, and active cancer. They say that the frequency of factors such as these may explain why it has proved difficult to demonstrate benefits of extended prophylactic anticoagulation in acutely ill hospital patients. By contrast, they note, the benefits are well established among patients undergoing orthopedic surgery, who represent "a generally younger and healthier patient population."
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Eleanor McDermid, Senior medwireNews Reporter